【摘要】 目的探讨金属蛋白酶抑制物-1(TIMP-1)及其金属蛋白酶(MMP)-2、MMP-9在TIMP-1转基因小鼠和正常小鼠肝脏自然衰老过程中的表达和作用。方法选择3、12和24月龄正常和TIMP-1转基因小鼠,采用HE和Masson染色,观察小鼠肝脏的组织病理学改变,用RT-PCR和Western blot法分别检测TIMP-1和MMP-2、MMP-9在不同月龄小鼠肝脏组织中的表达。测定3月龄小鼠肝脏中超氧化物歧化酶(SOD)、单胺氧化酶(MAO)活性及丙二醛含量。结果24月龄小鼠肝脏中有较多的脂肪变性和胶原沉积,TIMP-1的表达随小鼠月龄增加而增高,转基因小鼠的病变更明显。两组小鼠MMP-2和MMP-9的表达均无明显变化。3月龄转基因小鼠肝脏组织学结构和形态无明显改变,但SOD活性降低,MAO活性增高,丙二醛含量增高(P<0．05)。结论TIMP-1表达增高在肝脏衰老过程中可能起重要作用。更多还原

【Abstract】 Objective To investigate the expressions and role of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), matrix metalloproteinase-2 (MMP-2) and MMP-9 in the process of natural aging in normal and transgenic mice liver. Methods The normal and transgenic mice were divided into 3 groups: 3-month-old group (n=5), 12-month-old group (n = 5) and 24-month-old group (n = 5). Histopathological changes of liver were observed by HE and Masson stain. The mRNA levels of TIMP-1, MMP-2 and MMP-9 were determined by semi-quantitative reverse transcription -polymerase chain reaction (RT-PCR). The protein expression in livers of normal and transgenic mice from various ages was measured by Western blot. The activities of superoxide dismutase (SOD) and monoamine oxidase (MAO), content of malondialdehyde (MDA) as well as oxidative level and anti-oxidative ability were measured. Results Histologic examination showed that more fatty degeneration and collagen deposition were found in the liver of 24-month-old transgenic mice than those of the normal mice as their month ages increased. The mRNA and protein expressions of TIMP-1 were increased along with the increased month ages. When compared with the normal mice liver, the histopathological changes, the mRNA and protein expressions of TIMP-1 were increased significantly in transgenic mice liver. The expressions of MMP-2 and MMP-9 had little change in the process of aging. No liver change and collagen deposition was found in 3-month-old mice, but the activity of SOD decreased, and the activity of MAO and the content of MDA increased in transgenic mice liver (P<0. 05). Conclusions The expression of TIMP-1 is significantly high in transgenic mice liver with the process of aging, indicating that TIMP-1 may play an important role in the process of liver aging.更多还原